Biobehavioral models of approach and avoidance have been valuable in understanding vulnerability to depression but do not provide a sufficient explanation for the disorder. A critical component underemphasized in these models is the self-regulatory cognition that determines whether individuals see themselves as failing to make progress toward their goals. In this revised application for an R24 award under PAR-02-062 (Building Translational Research in Behavioral Science), we take a basic science approach to expanding the behavioral approach (BAS) and avoidance (BIS) systems by adding this critical cognitive component. The expanded BAS and BIS are referred to as self/brain/behavior systems, because the representation of personally salient goals and of one's progress toward those goals is hypothesized to be central to the function of each system. The basic predictions of our model are (a) that priming an individual's personally significant goals will lead to predictable changes in the neurophysiology of the BAS or BIS, and (b) that the effects of priming an individual's goals will differ according to the functional state of the relevant system, demonstrating a potential contributory role for self-regulatory failure in vulnerability to depression. Three basic study designs will be developed, each of which uses priming of personally significant goals as an independent variable: (1) determining the effects of presenting success and failure feedback for promotion vs. prevention goals on patterns of brain activation via fMRI; (2) examining sequences of information processing following success/failure feedback for promotion vs. prevention goals via measurement of event-related brain potentials; and (3) determining the impact of acute pharmacologic challenge with a dopamine receptor agonist on responses to priming of promotion or prevention goals. In turn, each design will be tested in three samples, each representing a hypothetical state of the expanded BAS: euthymic samples (representing a resilient state), at-risk samples (representing a vulnerable state), and depressed samples (representing a dysfunctional state). Analyzing data within and across samples will provide tests for both major predictions. This application is the first stage of a commitment to integrative translational research that may ultimately lead to clinical applications such as predicting vulnerability to depression, matching patients to treatments as a function of specific vulnerabilities, refining existing interventions, and developing new intervention/prevention strategies.